Although highly active antiretroviral therapy (HAART) has been successful in controlling plasma HIV levels it has not been able to eradicate HIV infection. In addition, the effects of HAART on immunologic restoration remains incomplete. HAART initiated during acute HIV infection may preserve HIV-specific CD4+ T cell responses that are thought to enhance HIV-specific CD8+ T cell function. The present study was designed to determine whether preserved HIV-specific immune responses are augmented by the administration of the immunomodulatory agent interleukin (IL)-2. Nine individuals recently (<6 months) infected with HIV were randomized to receive HAART alone or HAART plus 3 cycles of intermittent IL-2 during a 12 months period. Although HAART plus IL-2 significantly increased naive and absolute CD4+ T cell counts compared to HAART alone, there was no increase in CD4+ or CD8+ HIV-specific immune responses. In addition, adjuvant IL-2 therapy did not reduce the pool of HIV-infected resting CD4+ T cells. Thus, although intermittent IL-2 plus HAART quantitatively increases CD4+ T cells this increase is not selective for HIV-specific CD4+ or CD8+ T cell responses in recently infected individuals.